TY - JOUR
T1 - Age does matter in adolescents and young adults versus older adults with advanced melanoma; a national cohort study comparing tumor characteristics, treatment pattern, toxicity and response
AU - van der Kooij, Monique K.
AU - Wetzels, Marjolein J.A.L.
AU - Aarts, Maureen J.B.
AU - van den Berkmortel, Franchette W.P.J.
AU - Blank, Christian U.
AU - Boers-Sonderen, Marye J.
AU - Dierselhuis, Miranda P.
AU - de Groot, Jan Willem B.
AU - Hospers, Geke A.P.
AU - Piersma, Djura
AU - van Rijn, Rozemarijn S.
AU - Suijkerbuijk, Karijn P.M.
AU - Ten Tije, Albert J.
AU - van der Veldt, Astrid A.M.
AU - Vreugdenhil, Gerard
AU - Wouters, Michel W.J.M.
AU - Haanen, John B.A.G.
AU - van den Eertwegh, Alfonsus J.M.
AU - Bastiaannet, Esther
AU - Kapiteijn, Ellen
N1 - Publisher Copyright:
© 2020, MDPI AG. All rights reserved.
PY - 2020/8
Y1 - 2020/8
N2 - Cutaneous melanoma is a common type of cancer in Adolescents and Young Adults (AYAs, 15–39 years of age). However, AYAs are underrepresented in clinical trials investigating new therapies and the outcomes from these therapies for AYAs are therefore unclear. Using prospectively collected nation-wide data from the Dutch Melanoma Treatment Registry (DMTR), we compared baseline characteristics, mutational profiles, treatment strategies, grade 3–4 adverse events (AEs), responses and outcomes in AYAs (n = 210) and older adults (n = 3775) who were diagnosed with advanced melanoma between July 2013 and July 2018. Compared to older adults, AYAs were more frequently female (51% versus 40%, p = 0.001), and had a better Eastern Cooperative Oncology Group performance status (ECOG 0 in 54% versus 45%, p = 0.004). BRAF and NRAS mutations were age dependent, with more BRAF V600 mutations in AYAs (68% versus 46%) and more NRAS mutations in older adults (13% versus 21%), p < 0.001. This finding translated in distinct first-line treatment patterns, where AYAs received more initial targeted therapy. Overall, grade 3–4 AE percentages following first-line systemic treatment were similar for AYAs and older adults; anti-PD-1 (7% versus 14%, p = 0.25), anti-CTLA-4 (16% versus 33%, p = 0.12), anti-PD-1 + anti-CTLA-4 (67% versus 56%, p = 0.34) and BRAF/MEK-inhibition (14% versus 23%, p = 0.06). Following anti-CTLA-4 treatment, no AYAs experienced a grade 3–4 colitis, while 17% of the older adults did (p = 0.046). There was no difference in response to treatment between AYAs and older adults. The longer overall survival observed in AYAs (hazard ratio (HR) 0.7; 95% CI 0.6–0.8) was explained by the increased cumulative incidence of non-melanoma related deaths in older adults (sub-distribution HR 2.8; 95% CI 1.5–4.9), calculated by competing risk analysis. The results of our national cohort study show that baseline characteristics and mutational profiles differ between AYAs and older adults with advanced melanoma, leading to different treatment choices made in daily practice. Once treatment is initiated, AYAs and older adults show similar tumor responses and melanoma-specific survival.
AB - Cutaneous melanoma is a common type of cancer in Adolescents and Young Adults (AYAs, 15–39 years of age). However, AYAs are underrepresented in clinical trials investigating new therapies and the outcomes from these therapies for AYAs are therefore unclear. Using prospectively collected nation-wide data from the Dutch Melanoma Treatment Registry (DMTR), we compared baseline characteristics, mutational profiles, treatment strategies, grade 3–4 adverse events (AEs), responses and outcomes in AYAs (n = 210) and older adults (n = 3775) who were diagnosed with advanced melanoma between July 2013 and July 2018. Compared to older adults, AYAs were more frequently female (51% versus 40%, p = 0.001), and had a better Eastern Cooperative Oncology Group performance status (ECOG 0 in 54% versus 45%, p = 0.004). BRAF and NRAS mutations were age dependent, with more BRAF V600 mutations in AYAs (68% versus 46%) and more NRAS mutations in older adults (13% versus 21%), p < 0.001. This finding translated in distinct first-line treatment patterns, where AYAs received more initial targeted therapy. Overall, grade 3–4 AE percentages following first-line systemic treatment were similar for AYAs and older adults; anti-PD-1 (7% versus 14%, p = 0.25), anti-CTLA-4 (16% versus 33%, p = 0.12), anti-PD-1 + anti-CTLA-4 (67% versus 56%, p = 0.34) and BRAF/MEK-inhibition (14% versus 23%, p = 0.06). Following anti-CTLA-4 treatment, no AYAs experienced a grade 3–4 colitis, while 17% of the older adults did (p = 0.046). There was no difference in response to treatment between AYAs and older adults. The longer overall survival observed in AYAs (hazard ratio (HR) 0.7; 95% CI 0.6–0.8) was explained by the increased cumulative incidence of non-melanoma related deaths in older adults (sub-distribution HR 2.8; 95% CI 1.5–4.9), calculated by competing risk analysis. The results of our national cohort study show that baseline characteristics and mutational profiles differ between AYAs and older adults with advanced melanoma, leading to different treatment choices made in daily practice. Once treatment is initiated, AYAs and older adults show similar tumor responses and melanoma-specific survival.
KW - Adolescents
KW - Advanced melanoma
KW - AYA
KW - BRAF mutation
KW - Checkpoint inhibitors
KW - Clinical audit
KW - Outcome research
KW - Prospective nation-wide data
KW - Targeted therapy
KW - Young adults
UR - http://www.scopus.com/inward/record.url?scp=85089179148&partnerID=8YFLogxK
U2 - 10.3390/cancers12082072
DO - 10.3390/cancers12082072
M3 - Article
AN - SCOPUS:85089179148
VL - 12
SP - 1
EP - 15
JO - Cancers
JF - Cancers
IS - 8
M1 - 2072
ER -